Age Is a Key Factor Influencing the Choice of Treatment for Primary Patellar Dislocation: A Systematic Review and Meta-analysis.

Primary patellar dislocation has a certain recurrence rate after either conservative or surgical treatment, and the optimal treatment for patients with primary patellar dislocation of different ages remains unclear. This study aims to compare the clinical efficacy of surgical and conservative treatments for primary patellar dislocation across different age groups. According to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist, we conducted a systematic search for randomized controlled trials. We searched the PubMed, EMBASE, Cochrane Library, and Web of Science databases for randomized controlled trials of primary patellar dislocation treated surgically or conservatively up to January 2023. Data searching, extraction, analysis, and quality assessment were carried out in accordance with the Cochrane Collaboration guidelines. A total of nine studies with 433 patients were included in our study. There was no statistically significant difference between the two treatment modalities in terms of Kujala score, pain score, patient satisfaction, reoperation, and Tegner score. The rate of re-dislocation after surgical treatment is lower than that after conservative treatment. Subgroup analysis based on mean age showed that when the age was >20 years, Kujala scores were higher after surgical treatment than after conservative treatment (p < 0.0001, 95% confidence interval [CI] = 10.41-21.30). When the age was ≤20 years, the difference in Kujala scores between the two treatment modalities was not statistically significant. When the age was >20 years, the recurrence rate of patellar dislocation was lower after surgical treatment than after conservative treatment (p = 0.009, 95% CI = 0.08-0.70). When the age was ≤20 years, the difference in the recurrence rate of patellar dislocation between the two treatment modalities was not statistically significant. When the age of patients with primary patellar dislocation is ≤20 years, both surgical and conservative treatments result in similar clinical outcomes. When the age is >20 years, better clinical outcomes can be achieved by opting for surgical treatment. Therefore, surgery may be a better option for patients with primary patellar dislocation whose age is >20 years.

Percutaneous Intradiscal Radiofrequency Thermocoagulation Combined with Sinuvertebral Nerve Ablation for the Treatment of Discogenic Low Back Pain.

BACKGROUND: Percutaneous intervertebral radiofrequency thermocoagulation (PIRFT) and sinuvertebral nerve ablation (SVNA) are commonly used clinical treatments for discogenic low back pain (DLBP). However, they have been reported to have low efficacy rates of approximately 16.5%-26.5%, especially in the medium to long term. OBJECTIVES: To investigate whether PIRFT combined with SVNA can reduce pain and improve clinical outcomes in patients with DLBP. STUDY DESIGN: This is a prospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: Following the inclusion and exclusion criteria, 195 patients were enrolled in this study and randomly divided into 3 groups of 65 patients each and treated with PIRFT+SVNA, PIRFT, or SVNA. Postoperative follow-ups were done at one week, one month, 3 months, 6 months, and 12 months. The demographic characteristics, relevant surgical information, and observed complications of all groups were recorded. The efficacy of the surgeries was evaluated using the visual analog scale (VAS), Oswestry disability index (ODI), and modified Macnab criteria. RESULTS: In total, 167 patients, comprising 81 men and 86 women (aged 28-75 years), were included in this study and completed postoperative follow-ups. There were 54 patients in the combined PIRFT and SVNA (PIRFT+SVNA) group, 58 patients in the PIRFT group, and 55 patients in the SVNA group. All groups were comparable because there were no significant differences in gender, age, disease duration, follow-up time, surgical segments and presence of high-intensity zones of the groups (P > 0.05). In addition, the efficacy of the PIRFT+SVNA group was significantly higher than that of the PIRFT and SVNA groups as assessed by the modified Macnab criteria (P = 0.032). Surgery was successfully completed in all 3 groups, and VAS and ODI improved at all postoperative time points in all 3 groups compared to the preoperative scores. The differences between the VAS and ODI scores preoperation and 12 months postoperation were not statistically significant between all 3 groups. However, at one week, one month, 3 months, and 6 months after surgery, the VAS and ODI scores were lower in the PIRFT+SVNA group compared to the PIRFT and SVNA groups. The difference in VAS scores among the 3 groups was most significant at one week postoperation, and the difference in ODI scores was most significant at one month postoperation. The VAS and ODI improvement rates of the 3 groups showed significant improvement at one week, one month, 3 months, and 6 months postoperation (P < 0.05). There was no significant difference among the 3 groups at 12 months postoperation (P > 0.05). LIMITATIONS: This study was limited by its small sample size in a single-center study. CONCLUSIONS: In DLBP, the sinuvertebral nerve (SVN) is the main nerve involved in the lumbar disc pain signaling pathway, and compared with PIRFT and SVNA alone, combined PIRFT and SVNA treatment may provide more satisfactory pain relief and functional improvement at an early stage.

Diagnosis and treatment of anterior cruciate ligament injuries: Consensus of Chinese experts part II: Graft selection and clinical outcome evaluation.

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: "Graft Selection" and "Clinical Outcome Evaluation" during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive "gold standard" graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

PGRMC2 influences the onset of postmenopausal osteoporosis through disulfidptosis in monocytes: Evidence from experimental validation and Mendelian randomization.

This study explores the role of disulfidptosis in monocytes and its relation to postmenopausal osteoporosis (PMOP). Using single-cell RNA sequencing and microarray assays, we identified key genes: LONRF1, ACAP2, IPO9, and PGRMC2. Through differential analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning, these genes were linked to PMOP. Functional enrichment and ROC curve analysis demonstrated their effectiveness in distinguishing postmenopausal fracture patients from healthy individuals. Notably, PGRMC2 exhibited significant expression differences, highlighted by a notable Area Under the Curve (AUC) value of 0.665. Further investigation involved Western blotting and immunohistochemical assays, revealing decreased PGRMC2 expression in ovariectomized (OVX) mice. This decrease was consistent across both experimental methods, emphasizing PGRMC2's role in PMOP. Moreover, PGRMC2 was predominantly present in macrophages compared to monocytes within bone tissue and was significantly located in bone marrow mesenchymal stem cells (BM-MSCs) in PMOP patients. It was also abundantly found in osteoblasts and adipocytes. Additionally, a Mendelian randomization analysis using the TwoSampleMR R package, with data from decode and GWAS databases, was conducted. This analysis showed a significant impact of PGRMC2 on osteoporosis risk (p = 0.0048, OR = 0.6836), suggesting a potential protective effect against the disease. Our results suggest that PGRMC2 may facilitate the differentiation of monocytes into macrophages in bone tissue, influencing the behavior of BM-MSCs. This, in turn, could impact the progression and severity of PMOP. The study provides new insights into the molecular mechanisms underlying postmenopausal osteoporosis and highlights the potential of PGRMC2 as a therapeutic target or biomarker for this condition.

Tissue engineering strategies hold promise for the repair of articular cartilage injury.

Articular cartilage damage and wear can result in cartilage degeneration, ultimately culminating in osteoarthritis. Current surgical interventions offer limited capacity for cartilage tissue regeneration and offer only temporary alleviation of symptoms. Tissue engineering strategies are increasingly recognized as promising modalities for cartilage restoration. Currently, various biological scaffolds utilizing tissue engineering materials are extensively employed in both fundamental and clinical investigations of cartilage repair. In order to optimize the cartilage repair ability of tissue engineering scaffolds, researchers not only optimize the structure and properties of scaffolds from the perspective of materials science and manufacturing technology to enhance their histocompatibility, but also adopt strategies such as loading cells, cytokines, and drugs to promote cartilage formation. This review provides an overview of contemporary tissue engineering strategies employed in cartilage repair, as well as a synthesis of existing preclinical and clinical research. Furthermore, the obstacles faced in the translation of tissue engineering strategies to clinical practice are discussed, offering valuable guidance for researchers seeking to address these challenges.

Cell-free decellularized skin matrix scaffolds: A promising approach for meniscus regeneration in a rabbit meniscectomy model.

Tissue engineering presents a promising approach for the treatment of meniscal injuries, yet the development of meniscal scaffolds that exhibit both superior biomechanical properties and biocompatibility remains a considerable challenge. In this study, decellularized skin matrix (DSM) scaffolds were first prepared using porcine skin through decellularization and freeze-drying techniques. The DSM scaffold has favorable porosity, hydrophilicity, and biocompatibility. Importantly, the collagen content and tensile modulus of the scaffold are comparable to those of native meniscus (44.13 ± 2.396 mg/g vs. 42.41 ± 2.40 mg/g and 103.30 ± 2.98 MPa vs. 128.80 ± 9.115 MPa). Subsequently, the peptide PFSSTKT (PFS) with mesenchymal stem cells (MSCs) recruitment capability was used to modify DSM to construct DSM-PFS scaffolds. Compared to the DSM scaffold, the optimized DSM-PFS scaffold enhanced in vitro collagen and glycosaminoglycan (GAG) production and upregulated the expression of cartilage-specific genes. Furthermore, the DSM-PFS scaffold was more effective in recruiting MSCs in vitro. In vivo studies in rabbit models showed that the DSM-PFS scaffold successfully promoted meniscus tissue regeneration. Three months post-implantation, meniscus tissue formation can be observable, and after six months, the neo-meniscus exhibited tissue structure and tensile properties similar to the native meniscus. Notably, the DSM-PFS scaffold exhibited significant chondroprotective effects, slowing osteoarthritis (OA) progression. In conclusion, the DSM-PFS scaffold may represent a promising candidate for future applications in meniscus tissue engineering. STATEMENT OF SIGNIFICANCE: We developed a decellularized skin matrix (DSM) meniscus scaffold using whole-layer porcine skin, demonstrating superior biomechanical strength and biocompatibility. Following modification with the stem cell-recruiting peptide PFS, the optimized DSM-PFS scaffold outperformed the DSM scaffold in cell attraction, collagen and glycosaminoglycan production, and cartilage-specific gene expression. Implanted into rabbit knee joints, the cell-free DSM-PFS scaffold induced meniscal tissue formation within three months, achieving the histological structure and tensile strength of the native meniscus by six months. Moreover, it significantly protected the cartilage. Our findings provide new insights into the fabrication of scaffolds for meniscal tissue engineering, with the DSM-PFS scaffold emerging as an ideal candidate for future applications.

IL-16 Mediates the Effect of Circulating Metabolites on Postmenopausal Osteoporosis: A Two-Step, Multivariable Mendelian Randomization Study.

Objectives: This study aimed to explore the relationship between circulating metabolites and postmenopausal osteoporosis (PMOP) and to assess the mediating role of inflammatory factors. Methods: Utilizing summary-level data from genome-wide association studies (GWAS) and employing a Mendelian Randomization approach, a two-sample MR analysis was conducted to assess the relationship between circulating metabolites and PMOP. Additionally, a two-step MR was used to quantify the mediating impact of inflammatory factors on the effect of circulating metabolites on PMOP. Results: The results revealed a significant association between certain metabolites and the risk of PMOP, notably the ratio of free cholesterol to total lipids in very large VLDL particles (OR: 1.399, 95% CI: 1.002-1.954, p = 0.048) and IL-16 (OR: 0.773, 95% CI: 0.608-0.983, p = 0.036). IL-16 was found to partially mediate the impact of circulating metabolites on PMOP, with a mediation effect of 10.4%. Conclusion: This study underscores the crucial role of circulating metabolites and inflammatory factors in PMOP pathogenesis. A causal relationship between circulating metabolites and PMOP was established, with IL-16 mediating some effects. These findings hold promise for clinical applications in early detection, personalized medicine, and the identification of therapeutic targets for PMOP.

Sirt1: An Increasingly Interesting Molecule with a Potential Role in Bone Metabolism and Osteoporosis.

Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass, decreased bone mineral density, and degradation of bone tissue microarchitecture. However, our understanding of the mechanisms of bone remodeling and factors affecting bone mass remains incomplete. Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase that regulates a variety of cellular metabolisms, including inflammation, tumorigenesis, and bone metabolism. Recent studies have emphasized the important role of SIRT1 in bone homeostasis. This article reviews the role of SIRT1 in bone metabolism and OP and also discusses therapeutic strategies and future research directions for targeting SIRT1.

Machine-Learning Models Reliably Predict Clinical Outcomes in Medial Patellofemoral Ligament Reconstruction.

PURPOSE: To develop a machine-learning model to predict clinical outcomes after medial patellofemoral ligament reconstruction (MPFLR) and identify the important predictive indicators. METHODS: This study included patients who underwent MPFLR from January 2018 to December 2022. The exclusion criteria were as follows: (1) concurrent bony procedures, (2) history of other knee surgeries, and (3) follow-up period of less than 12 months. Forty-two predictive models were constructed for 7 clinical outcomes (failure to achieve minimum clinically important difference of clinical scores, return to preinjury sports, pivoting sports, and recurrent instability) using 6 machine-learning algorithms (random forest, logistic regression, support vector machine, decision tree, implemented multilayer perceptron, and K-nearest neighbor). The performance of the model was evaluated using metrics such as the area under the receiver operating characteristic curve, accuracy, specificity, and sensitivity. In addition, SHapley Additive exPlanation summary plot was employed to identify the important predictive factors of the best-performing model. RESULTS: A total of 218 patients met criteria. For the best-performing models in predicting failure to achieve the minimum clinically important difference for Lysholm, International Knee Documentation Committee, Kujala, and Tegner scores, the area under the receiver operating characteristic curves and accuracies were 0.884 (good) and 87.3%, 0.859 (good) and 86.2%, 0.969 (excellent) and 97.0%, and 0.760 (fair) and 76.8%, respectively; 0.952 (excellent) and 95.2% for return to preinjury sports; 0.756 (fair) and 75.4% for return to pivoting sports; and 0.943 (excellent) and 94.9% for recurrent instability. Low preoperative Tegner score, shorter time to surgery, and absence of severe trochlear dysplasia were significant predictors for return to preinjury sports, whereas the absence of severe trochlear dysplasia and patellar alta were significant predictors for return to pivoting sports. Older age, female sex, and low preoperative Lysholm score were highly predictive of recurrent instability. CONCLUSIONS: The predictive models developed using machine-learning algorithms can reliably forecast the clinical outcomes of MPFLR, particularly demonstrating excellent performance in predicting recurrent instability. LEVEL OF EVIDENCE: Level III, case-control study.

Fluid shear stress-mediated Piezo1 alleviates osteocyte apoptosis by activating the PI3K/Akt pathway.

Glucocorticoid-induced osteoporosis serves as a primary cause for secondary osteoporosis and fragility fractures, representing the most prevalent adverse reaction associated with prolonged glucocorticoid use. In this study, to elucidate the impact and underlying mechanisms of fluid shear stress (FSS)-mediated Piezo1 on dexamethasone (Dex)-induced apoptosis, we respectively applied Dex treatment for 6 h, FSS at 9 dyne/cm2 for 30 min, Yoda1 treatment for 2 h, and Piezo1 siRNA transfection to intervene in MLO-Y4 osteocytes. Western blot analysis was used to assess the expression of Cleaved Caspase-3, Bax, Bcl-2, and proteins associated with the PI3K/Akt pathway. Additionally, qRT-PCR was utilized to quantify the mRNA expression levels of these molecules. Hoechst 33258 staining and flow cytometry were utilized to evaluate the apoptosis levels. The results indicate that FSS at 9 dyne/cm2 for 30 min significantly upregulates Piezo1 in osteocytes. Following Dex-induced apoptosis, the phosphorylation levels of PI3K and Akt are markedly suppressed. FSS-mediated Piezo1 exerts a protective effect against Dex-induced apoptosis by activating the PI3K/Akt pathway. Additionally, downregulating the expression of Piezo1 in osteocytes using siRNA exacerbates Dex-induced apoptosis. To further demonstrate the role of the PI3K/Akt signaling pathway, after intervention with the PI3K pathway inhibitor, the activation of the PI3K/Akt pathway by FSS-mediated Piezo1 in osteocytes was significantly inhibited, reversing the anti-apoptotic effect. This study indicates that under FSS, Piezo1 in MLO-Y4 osteocytes is significantly upregulated, providing protection against Dex-induced apoptosis through the activation of the PI3K/Akt pathway.

Gut-bone axis research: unveiling the impact of gut microbiota on postmenopausal osteoporosis and osteoclasts through Mendelian randomization.

Background: Postmenopausal osteoporosis is a prevalent disease that affects the bone health of middle-aged and elderly women. The link between gut microbiota and bone health, known as the gut-bone axis, has garnered widespread attention. Methods: We employed a two-sample Mendelian randomization approach to assess the associations between gut microbiota with osteoclasts and postmenopausal osteoporosis, respectively. Single nucleotide polymorphisms associated with the composition of gut microbiota were used as instrumental variables. By analyzing large-scale multi-ethnic GWAS data from the international MiBioGen consortium, and combining data from the eQTLGen consortium and the GEFOS consortium, we identified microbiota related to osteoclasts and postmenopausal osteoporosis. Key genes were further identified through MAGMA analysis, and validation was performed using single-cell data GSE147287. Results: The outcomes of this study have uncovered significant associations within the gut microbiome community, particularly with the Burkholderiales order, which correlates with both an increase in osteoclasts and a reduced risk of postmenopausal osteoporosis. with an odds ratio (OR) of 0.400, and a P-value of 0.011. Further analysis using single-cell data allowed us to identify two key genes, FMNL2 and SRBD1, that are closely linked to both osteoclasts and osteoporosis. Conclusion: This study utilizing Mendelian randomization and single-cell data analysis, provides new evidence of a causal relationship between gut microbiota and osteoclasts, as well as postmenopausal osteoporosis. It was discovered that the specific microbial group, the Burkholderiales order, significantly impacts both osteoporosis and osteoclasts. Additionally, key genes FMNL2 and SRBD1 were identified, offering new therapeutic strategies for the treatment of postmenopausal osteoporosis.

Single Versus Double Tunnel Fixation in Medial Patellofemoral Ligament Reconstruction: A Meta-Analysis.

The purpose of this meta-analysis was to conduct a comparative analysis of clinical scores and complication rates among patients experiencing recurrent patellar dislocation who underwent medial patellofemoral ligament (MPFL) reconstruction using both single and double tunnel techniques. A comprehensive search was conducted across electronic databases including PubMed, the Cochrane Library, Web of Science, and Google Scholar to retrieve articles relevant to MPFL reconstruction utilising the tunnel technique. Subsequently, meta-analyses were undertaken to assess complication rates and changes in clinical scores before and after surgery. Following this, sensitivity analysis and meta-regression analysis were performed to scrutinise potential confounding variables. A total of thirty-two studies were included in the analysis, comprising twenty-seven non-comparative studies and five comparative studies. The findings revealed a similarity in postoperative complication rates between the single and double tunnel fixation techniques: [9.0% (95%CI, 4.0%-15.6%) versus 8.9% (95%CI, 4.7%-14.1%, p = 0.844)]. Likewise, no statistically significant differences were observed in Lysholm scores [34.1 (95%CI, 26.7-41.5) versus 33.8 (95%CI, 27.7-40.0, p = 0.956)], Kujala scores [29.4 (95%CI, 22.3-36.4) versus 27.3 (95%CI, 22.3-32.3, p = 0.637)], and Tegner score change [1.1 (95%CI, 0.8-1.4) versus 0.7 (95%CI, -0.2-1.6, p = 0.429)] before and after MPFL reconstruction, respectively, using these two techniques. In conclusion, the authors found that the clinical functional improvement and complication rates in MPFL reconstruction using the single tunnel fixation technique are comparable to those achieved with the double tunnel fixation approach. However, to further advance the understanding in this field, additional randomised controlled studies must be conducted to provide further insights. Key Words: MPFL reconstruction, Bone tunnel, Patellar dislocation, Meta-analysis.

Bone and Extracellular Signal-Related Kinase 5 (ERK5).

Bones are vital for anchoring muscles, tendons, and ligaments, serving as a fundamental element of the human skeletal structure. However, our understanding of bone development mechanisms and the maintenance of bone homeostasis is still limited. Extracellular signal-related kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, plays a critical role in the pathogenesis and progression of various diseases, especially neoplasms. Recent studies have highlighted ERK5's significant role in both bone development and bone-associated pathologies. This review offers a detailed examination of the latest research on ERK5 in different tissues and diseases, with a particular focus on its implications for bone health. It also examines therapeutic strategies and future research avenues targeting ERK5.

The development and external validation of a web-based nomogram for predicting overall survival with Ewing sarcoma in children.

Background: Ewing sarcoma remains the second most prevalent primary aggressive bone tumor in teens and young adults. The aim of our study was to develop and validate a web-based nomogram to predict the overall survival for Ewing sarcoma in children. Methods: A total of 698 patients, with 640 cases from the Surveillance, Epidemiology, and End Results (the training set) and 58 cases (the external validation set), were included in this study. Cox analyses were carried out to determine the independent prognostic indicators, which were further included to establish a web-based nomogram. The predictive abilities were tested through the concordance index, calibration curve, decision curve analysis, and area under the receiver operating characteristic curve. Results: As suggested by univariate and multivariate Cox analyses, age, primary site, tumor size, metastasis stage (M stage), and chemotherapy were included as the independent predictive variables. The area under the receiver operating characteristic curve values, calibration curves, concordance index, and decision curve analysis from training and validation groups suggested the model has great clinical applications. Conclusion: We developed a convenient and precise web-based nomogram to evaluate overall survival for Ewing sarcoma in children. The application of this nomogram would assist physicians and patients in making decisions.

Do Age and Timing Influence the Outcomes of Single-stage Reconstruction of Multiple Ligament Knee Injuries? 5-10 Years Follow Up.

OBJECTIVES: Multiple ligament knee injuries (MLKIs) are disruptive injuries, however, there are controversies in the results of acute and delayed reconstruction. Also, clinical outcomes between patients older or younger than 40 have not been compared in MLKIs. This study was designed to investigate the influence of age and timing of reconstruction on the outcomes of single-stage reconstruction of MLKIs. METHODS: The patients who underwent reconstruction of multiple injured ligaments because of MLKIs between May 2013 and July 2019 were added to the cohort. The postoperative complications, knee range of motion (ROM), Lysholm score, International Knee Documentation Committee (IKDC) 2000 score, Tegner activity level, patient satisfaction, and SF-36 score were compared between young (≤ 40 years old, n = 41) and old patients (n = 61); acute (≤ 3 weeks after injury, n = 75) and delayed reconstruction (n = 27), using Mann-Whitney U test or χ2 test. RESULTS: A total of 102 MLKI patients managed by single-stage multi-ligament reconstruction were retrospectively reviewed. Patients were followed up after surgery for a mean of 7.3 years (5.2-10.7 years). At the last follow-up, no significant difference was found in knee ROM, functional scores, and patient-reported outcomes between patients older or younger than 40; acute and delayed reconstruction (p > 0.05). The rate of complications in the delayed reconstruction group was higher than that of the acute reconstruction group (22.2% vs 5.3%, p < 0.05). The IKDC objective scores reached grade A in 63.7%-80.4% of patients, and grade B in 11.8%-23.5% patients. CONCLUSION: The single-stage reconstruction of MLKIs can obtain comparative long-term functional and objective outcomes regardless of patients older or younger than 40; acute and delayed reconstruction, however, delayed reconstruction is related to a high rate of postoperative complications.

Unraveling Key m6A Modification Regulators Signatures in Postmenopausal Osteoporosis through Bioinformatics and Experimental Verification.

OBJECTIVE: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis-derived BMSCs (OP-BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6-methyladenosine RNA binding protein 3) on the osteogenic traits of OP-BMSCs and identify potential therapeutic targets to boost their bone formation ability. METHODS: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m6A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single-cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene. RESULTS: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single-cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP-BMSCs substantially impedes their proliferation and differentiation. CONCLUSION: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP-BMSCs.

Decreased sagittal slope of the medial tibial spine and deep concavity of the lateral tibial spine are risk factors for noncontact anterior cruciate ligament injury.

PURPOSE: This study aimed to assess the relationship between the geometric features of tibial eminence and susceptibility to noncontact anterior cruciate ligament (ACL) injuries. METHODS: Patients with unilateral noncontact knee injuries between 2015 and 2021 were consecutively enroled in this study. Based on knee magnetic resonance imaging (MRI) and arthroscopic visualisation, patients were categorised into the case group (ACL rupture) and control group (ACL intact). Using MRI, the geometric features of tibial eminence were characterised by measuring the sagittal slopes, depth of concavity and coronal slopes of the inclined surfaces of the tibial spines. Univariate and multivariate logistic regressions were conducted to explore independent associations between quantified geometric indices of tibial eminence and the risk of noncontact ACL injuries. RESULTS: This study included 187 cases and 199 controls. A decreased sagittal slope of the medial tibial spine (MTSSS) (combined group: odds ratio [OR]: 0.87 [0.82, 0.92], p < 0.001; females: OR: 0.88 [0.80, 0.98], p = 0.020; males: OR: 0.87 [0.81, 0.93], p < 0.001) and an increased depth of concavity in the lateral tibial spine (LTSD) (combined group: OR: 1.51 [1.24, 1.85], p < 0.001; females: OR: 1.65 [1.12, 2.43], p = 0.012; males: OR: 1.44 [1.11, 1.89], p = 0.007) were independent risk factors for noncontact ACL injuries. Moreover, a steeper coronal slope of the inclined surface of the medial tibial spine was a significant predictor of noncontact ACL injuries for males (MTSCS: OR: 1.04 [1.01, 1.08], p = 0.015) but not for females. CONCLUSION: Geometric features of tibial eminence, particularly a decreased MTSSS and an increased LTSD, were identified as independent risk factors for noncontact ACL injuries. These findings will help clinicians identify individuals at high risk of ACL injury and facilitate the development of targeted prevention strategies. LEVEL OF EVIDENCE: Level III.

METTL3-mediated m6A modification increases Hspa1a stability to inhibit osteoblast aging.

Senile osteoporosis is mainly caused by osteoblasts attenuation, which results in reduced bone mass and disrupted bone remodeling. Numerous studies have focused on the regulatory role of m6A modification in osteoporosis; however, most of the studies have investigated the differentiation of bone marrow mesenchymal stem cells (BMSCs), while the direct regulatory mechanism of m6A on osteoblasts remains unknown. This study revealed that the progression of senile osteoporosis is closely related to the downregulation of m6A modification and methyltransferase-like 3 (METTL3). Overexpression of METTL3 inhibits osteoblast aging. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that METTL3 upregulates the stability of Hspa1a mRNA, thereby inhibiting osteoblast aging. Moreover, the results demonstrated that METTL3 enhances the stability of Hspa1a mRNA via m6A modification to regulate osteoblast aging. Notably, YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) participates in stabilizing Hspa1a mRNA in the METTL3-mediated m6A modification process, rather than the well-known degradation function. Mechanistically, METTL3 increases the stability of Hspa1a mRNA in a YTHDF2-dependent manner to inhibit osteoblast aging. Our results confirmed the significant role of METTL3 in osteoblast aging and suggested that METTL3 could be a potential therapeutic target for senile osteoporosis.